Drosophila melanogaster models of MPS IIIC (Hgsnat-deficiency) highlight the role of glia in disease presentation.

Sanfilippo syndrome (Mucopolysaccharidosis type III or MPS III) is a recessively inherited neurodegenerative lysosomal storage disorder. Mutations in genes encoding enzymes in the heparan sulphate degradation pathway lead to the accumulation of partially degraded heparan sulphate, resulting ultimately in the development of neurological deficits. Mutations in the gene encoding the membrane protein heparan-α-glucosaminide N-acetyltransferase (HGSNAT; EC2.

Development of the ethmoid in a wallaby and implications for the homology of turbinal elements in marsupials.

The homologies of the turbinals (scroll bones) of the ethmoid are not well understood, including the potential implication for understanding mammalian phylogeny. Here we examine the postnatal development of this anatomical system in a marsupial mammal because previous work has shown that the adult pattern of five endoturbinals (ethmoturbinals) and two ectoturbinals (frontoturbinals) is conserved. Furthermore, marsupial phylogeny is fairly well resolved and provides a solid evolutionary framework for examining turbinal homologies.

Spherulitic Lead Calcium Apatite Minerals in Lead Water Pipes Exposed to Phosphate-Dosed Tap Water.

Phosphate dosing is the principle strategy used in the United Kingdom to reduce the concentration of lead in tap waters supplied by lead water pipes. The mechanisms of phosphate-mediated lead control are not fully understood, but solid solutions of lead calcium apatite are thought to play an important role. This study investigated the microstructure of a lead pipe, supplied with high-alkalinity tap water, in which the lead calcium apatite crystals were spherulitic having rounded and dumb-bell-shaped morphologies.

Kinetics of Metastable Argon Optical Excitation and Gain in Ar/He Microplasmas.

The optically pumped rare-gas metastable laser is capable of high-intensity lasing on a broad range of near-infrared transitions for excited-state rare gas atoms (Ar*, Kr*, Ne*, Xe*) diluted in flowing He. The lasing action is generated by photoexcitation of the metastable atom to an upper state, followed by collisional energy transfer with He to a neighboring state and lasing back to the metastable state. The metastables are generated in a high-efficiency electric discharge at pressures of ∼0.

The ovine Type II Gaucher disease model recapitulates aspects of human brain disease.

Acute neuronopathic (type II) Gaucher disease (GD) is a devastating, untreatable neurological disorder resulting from mutations in the glucocerebrosidase gene (GBA1), with subsequent accumulation of glucosylceramide and glucosylsphingosine. Patients experience progressive decline in neurological function, with onset typically within the first three-to-six months of life and premature death before two years. Mice and drosophila with GD have been described, however little is known about the brain pathology observed in the naturally occurring ovine model of GD.

Lysosomal gene displays haploinsufficiency in a knock-in mouse model of Alzheimer's disease.

Lysosomal network abnormalities are an increasingly recognised feature of Alzheimer's disease (AD), which appear early and are progressive in nature. Sandhoff disease and Tay-Sachs disease (neurological lysosomal storage diseases caused by mutations in genes that code for critical subunits of β-hexosaminidase) result in accumulation of amyloid-β (Aβ) and related proteolytic fragments in the brain. However, experiments that determine whether mutations in genes that code for β-hexosaminidase are risk factors for AD are currently lacking.

Production and loss of O(Δ ) at atmospheric pressure using microwave-driven microplasmas.

We have used arrays of microwave-generated microplasmas operating at atmospheric pressure to generate high concentrations of singlet molecular oxygen, O(Δ ), which is of interest for biomedical applications. The discharge is sustained by a pair of microstrip-based microwave resonator arrays which force helium/oxygen gas mixtures through a narrow plasma channel. We have demonstrated the efficacy of both NO and less-hazardous NO additives for suppression of ozone and associated enhancement of the O(Δ ) yield.

Crisis responses, opportunity, and public authority during Covid-19's first wave in Uganda, the Democratic Republic of Congo, and South Sudan.

Discussions on African responses to Covid-19 have focused on the state and its international backers. Far less is known about a wider range of public authorities, including chiefs, humanitarians, criminal gangs, and armed groups. This paper investigates how the pandemic provided opportunities for claims to and contests over power in Uganda, the Democratic Republic of the Congo, and South Sudan.

Is SGSH heterozygosity a risk factor for early-onset neurodegenerative disease?

Lysosomal dysfunction may be an important factor in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). Heterozygous mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) have been found in PD patients, and some but not all mutations in other lysosomal enzyme genes, for example, NPC1 and MCOLN1 have been associated with PD. We have examined the behaviour and brain structure of mice carrying a D31N mutation in the sulphamidase (Sgsh) gene which encodes a lysosomal sulphatase.

Evaluation of winter pressures on general practice in Manchester: a cross-sectional analysis of nine GP practices.

Background: The Nuffield Trust's report on NHS winter pressures highlights a lack of data for primary care, with a consequential focus on secondary care. An increase in data is required on the scale of the winter demand on primary care, so the need for investment in this area can be clearly seen.

Aim: To quantify seasonal variation in workload in primary and secondary care.

Evaluating the feasibility and impact of case rate payment for recovery support navigator services: a mixed methods study.

Background: Acute 24-h detoxification services (detox) are necessary but insufficient for many individuals working towards long-term recovery from opiate, alcohol or other drug addiction. Longer engagement in substance use disorder (SUD) treatment can lead to better health outcomes and reductions in overall healthcare costs. Connecting individuals with post-detox SUD treatment and supportive services is a vital next step.

Twelve tips for conducting a virtual OSCE.

Recently many medical schools have faced the challenge of redesigning their existing assessments to run in a virtual format. We ran a virtual Objective Structured Clinical Examination (OSCE) for a group of final year students assessing clinical communication skills, written communication, practical skills, examination skills and professionalism. OSCEs provide the opportunity to test skills that written papers cannot, so it was important to include such a clinical exam in the portfolio of assessments for graduating students.

A Comparative Effectiveness Study of Newborn Screening Methods for Four Lysosomal Storage Disorders.

Newborn screening for one or more lysosomal disorders has been implemented in several US states, Japan and Taiwan by multiplexed enzyme assays using either tandem mass spectrometry or digital microfluidics. Another multiplex assay making use of immunocapture technology has also been proposed. To investigate the potential variability in performance of these analytical approaches, we implemented three high-throughput screening assays for the simultaneous screening for four lysosomal disorders: Fabry disease, Gaucher disease, mucopolysaccharidosis type I, and Pompe disease.

Online patient simulation training to improve clinical reasoning: a feasibility randomised controlled trial.

Background: Online patient simulations (OPS) are a novel method for teaching clinical reasoning skills to students and could contribute to reducing diagnostic errors. However, little is known about how best to implement and evaluate OPS in medical curricula. The aim of this study was to assess the feasibility, acceptability and potential effects of eCREST - the electronic Clinical Reasoning Educational Simulation Tool.

Impact of recovery support navigators on continuity of care after detoxification.

Although evidence points to the benefits of continuity of care after detoxification (detox), especially when continuity of care occurs within a short time after discharge from a detox episode, the rate at which clients engage in continued treatment after detox remains low. The goal of the study was to develop and deploy a specially trained workforce, called recovery support navigators (RSNs), to increase the likelihood of clients continuing onto treatment after detox. Continuity of care is defined as receiving any substance use disorder (SUD) treatment service within 14 days of discharge from the index detox.

Lysosomal Dysregulation in the Murine App Model of Alzheimer's Disease.

Lysosomal network dysfunction is a prominent feature of Alzheimer's disease (AD). Although transgenic mouse models of AD are known to model some aspects of lysosomal network dysfunction, the lysosomal network has not yet been examined in the knock-in App mouse. We aimed to determine whether App mice exhibit disruptions to the lysosomal network in the brain.

Chemically transformed monolayers on acene thin films for improved metal/organic interfaces.

Anhydride terminated acene thin films were chemically transformed to thiol or carboxylic acid functionalities, groups heretofore incompatible with monolayer reactions. The molecular surface imparts large rate acceleration when imides are formed, while disfavored disulfides can be formed from the thiols. The modified surface imparts improved adhesion to top metal contacts in flexible/bendable applications.

Designing and developing a co-produced theoretical and evidence-based online support for family caregivers of people with dementia at the end of life.

Background: Caring for someone with dementia can be physically and emotionally difficult. Acting as a caregiver can make it difficult to access sources of support, particularly in the later stages of dementia. This paper reports the development and presents the targets (subject areas) and components of a prototype website to support family caregivers of a person with dementia towards the end of life.

The key aspects of online support that older family carers of people with dementia want at the end of life: A qualitative study.

Family carers towards the end of life face a range of difficult challenges and have high levels of support needs. The aim of this study was to explore the challenges carers of people with dementia face towards the end of life and the support needs which could be addressed by online support. Qualitative study using semi-structured interviews with 23 current and former family carers of people with dementia in England in 2016-2017.

Synthetic Disaccharide Standards Enable Quantitative Analysis of Stored Heparan Sulfate in MPS IIIA Murine Brain Regions.

Heparan sulfate (HS) is a complex polysaccharide from the glycosaminoglycan (GAG) family that accumulates in tissues in several neurological lysosomal storage diseases known as mucopolysaccharidosis (MPS) disorders. The quantitation of HS in biological samples is important for studying MPS disorders but is very challenging because of its high molecular weight and heterogeneity. Recently, acid-catalyzed butanolysis followed by LC-MS/MS analysis has emerged as a promising method for the determination of HS.

Technology for Augmenting Type 1 Diabetes Mellitus Management.

Type 1 diabetes mellitus has witnessed significant progress in its management over the past several decades. This review highlights technologic advancements in type 1 diabetes management. Continuous glucose monitoring systems are now available at various functionality and cost levels, addressing diverse patient needs, including a recently US Food and Drug Administration (FDA)-approved implantable continuous glucose monitoring system (CGMS).

Cost Savings from a Navigator Intervention for Repeat Detoxification Clients.

Background: Many clients with substance use disorders (SUD) have multiple admissions to a 24-hour level of care for detoxification without ever progressing to SUD treatment. In the US, health insurers have become concerned about the high costs and ineffective results of repeat detox admissions. For other diseases, health systems increasingly target high-risk, high-cost patients with individually tailored interventions delivered by `navigators' who help patients negotiate the complex health care system.

Early disease course is unaltered in mucopolysaccharidosis type IIIA (MPS IIIA) mice lacking α-synuclein.

Background: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is an inherited paediatric-onset neurodegenerative disorder caused by the lysosomal deficiency of sulphamidase with subsequent accumulation of heparan sulphate. The pathological mechanisms responsible for clinical disease are unknown; however, intraneuronal accumulation of aggregation-prone proteins such as α-synuclein, phosphorylated tau and amyloid precursor protein suggests inefficient intracellular trafficking and lysosomal degradation.

Aim: To investigate the contribution the accumulating α-synuclein plays in early symptom emergence that is, impaired cognition, reduced anxiety and motor deficits, first detectable between 3-5 months of age.

Wave Propagation in Composites of Plasma and Metamaterials with Negative Permittivity and Permeability.

Wave propagation is observed through a negative permeability metamaterial immersed in gaseous plasma. A 3D array of split ring resonators (SRR) is enveloped by an inductively heated argon plasma with a nominal plasma frequency of 2.65 GHz.